Dispersible antibody compositions and methods for their preparation and use

• US 6,514,496 B1
• Filed: 03/21/2000
• Issued: 02/04/2003
• Est. Priority Date: 04/14/1995
• Status: Expired due to Fees

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Inhale Therapeutics Systems Inc (Nektar Therapeutics)
• Inventors: Foster, Linda C., Patton, John S., Platz, Robert M., Eljamal, Mohammed
• Primary Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US09/531,183
• Time in Patent Office: 1,050 Days
• Field of Search: 424/130.1, 514/951
• US Class Current: 424/130.1
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61M 15/0086 Inhalation chambers

Abstract

This invention relates to dispersible antibody compositions and methods for preparing and using these compositions. In particular, the present invention relates to dry powder dispersible antibody compositions wherein antibody conformation is preserved. The compositions have good powder dispersibility and other desirable characteristics for pulmonary delivery of therapeutic antibodies.

Claims

1. An antibody-based dry powder composition for pulmonary comprising a predetermined amount of antibody which is non-aggregated and is in its native conformation in respirable dry powder particles, wherein said composition has a delivered dose efficiency of at least about 30%.

2. The composition of claim 1 which is dispersible.

3. The composition of claim 1 which further comprises a pharmaceutically acceptable excipient or carrier.

4. The composition of claim 3 wherein the carrier or excipient is selected from the group consisting of sugars, alditols, organic salts, amino acids, polymers, proteins and peptides.

5. The composition of claim 1 wherein the antibody comprises at least about 40% by weight of the composition.

6. The composition of claim 1 wherein the particles in the powder have a particle size range of from about 0.4 μ

m to about 5 μ

mm MMD.

7. The composition of claim 1 wherein the particles have an MMAD of less than about 5μ

m.

8. The composition of claim 1 which contains less than about 10% by weight moisture.

9. A method for preparing the composition of claim 1 comprising:

a) mixing the antibody with a solvent to form a solution or suspension; and

b) spray drying the mixture formed in step a) under conditions which provide a respirable dry powder, wherein the antibody is non-aggregated and is in its native conformation.

10. The method of claim 9 further comprising the step of adding a pharmaceutically acceptable excipient or carrier prior to spray drying.

11. The method of claim 9 wherein the solvent is selected from the group consisting of water and ethanol.

12. A method of treating a condition in an animal which condition may be alleviated by an antibody, the method comprising pulmonary administration of a therapeutically effective amount of the composition of claim 1 to an animal susceptible to or suffering from the condition.

13. The method of claim 12 wherein the method is used to treat a condition selected from the group consisting of inflammation, allergy, cancer, bacterial infection and viral infection.

14. An antibody-based dry powder composition for pulmonary delivery comprising a predetermined amount of antibody which is non-aggregated and is in its native conformation in respirable dry powder particles wherein the antibody is selected from the group consisting of IgG, IgA and IgM.

15. The composition of claim 14 which is dispersible.

16. The composition of claim 14 which further comprises a pharmaceutically acceptable excipient or carrier.

17. The composition of claim 16 wherein the carrier or excipient is selected from the group consisting of sugars, alditols, organic sales, amino acids, polymers, proteins and peptides.

18. The composition of claim 14 wherein the antibody comprises at least about 40% by weight of the composition.

19. The composition of claim 14 wherein the particles in the powder have a particle size range of from about 0.4 μ

m to about 5 μ

mm MMD.

20. The composition of claim 14 wherein the particles have an MMAD of less than about 5 μ

m.

21. The composition of claim 14 which contains less than about 10% by weight moisture.

22. The composition of claim 14 which has a delivered dose efficiency of at least about 30%.

23. A method for preparing the composition of claim 14 comprising:

a) mixing the antibody with a solvent to form a solution or suspension; and

b) spray drying the mixture formed in step a) under conditions which provide a respirable dry powder, wherein the antibody is non-aggregated and is in its native conformation.

24. The method of claim 23 further comprising the step of adding a pharmaceutically acceptable excipient or carrier prior to spray drying.

25. The method of claim 23 wherein the solvent is selected from the group consisting of water and ethanol.

26. A method of treating or preventing a condition in an animal which condition may be prevented or alleviated by an antibody, the method comprising pulmonary administration of a therapeutically effective amount of the composition of claim 14 to an animal susceptible to or suffering from the condition.

27. The method of claim 26 wherein the method is used to treat a condition selected from the group consisting of inflammation, allergy, cancer, bacterial infection and viral infection.